Some
months ago, I read a new biography of Leonardo da Vinci and one of the
facts that interested me most about this Renaissance giant was that
one of his favourite mottos was "Ostinato Rigore".

Undoubtedly,
that idea of unrelenting rigor marked the life of this brilliant artist,
scientist, hydraulic and military engineer. Leonardo looked for perfection
and beauty with such obstinacy that it caused him great suffering and
limited the number of his incredible works.

We
could propose a definition for rigor saying that it consists in the
disciplined application of reason to subjects related to knowledge and
or communication.

Rigor
is many things. It is dissatisfaction with uncertainty, with inaccurate
answers, with unprecise measurements, with the spread between the plus
and the minus.

Rigor
is also being methodical commitment to experimental procedure, to the
need of controlling all parameters that can affect the results of our
tests.

But
rigor is also strict adherence to the truth, it is to disrobe ourselves
of our prejudices and enthusiasm when we interpret our results, it is
to search for all possible explanations of what we observe, it is accepting
a result that demonstrates the fallacy of our most precious hypothesis

Rigor
is an attitude that contrasts with the weaknesses of human nature, does
not allow laziness, the lack of attention, the acceptance of inexact
methods, the adoption of groundless conclusions, accepting the predominant
opinion despite the lack of data which sustain it. A famous biochemist,
Dr. Efraim Racker, once said “there’s nothing sadder that
an ugly fact destroying a beautiful idea”. Rigor demands us to
accept the destruction of that beautiful idea by facts.

Rigor
is in the essence of scientific work, in each one of the stages of the
research work. Rigor implies a structured and controlled way of planning,
developing, analyzing and evaluating our research and a special care
in adapting the presentation of the results to the demands of the audience
we communicate the results of our investigations.

Let’s
review step by step the stages of research and how rigor influences
them.

Investigations
start with questions that we ask ourselves about the universe, human
beings, and nature that surrounds us. Scientific questions are different
from the ones that philosophers or theologians ask themselves due to
the fact that the scientific questions can and should have experimental
answers.

In
the formulation of question(s), the rigor is precisely in achieving
precision in formulating the questions thus allowing us to imagine experiments
able to answer them. It is not enough to ask ourselves ‘What causes
cancer ?’ All the available information should be used to break
down that big question into a series of other related questions that
enable to obtain clear answers. For example ‘Why a serine 45 mutation
of the beta catenine protein is frequently found in many tumours?’

When
making this question, the rigorous scientist will have one hypothesis,
a possible answer that can be experimentally checked and that will answer
the question. For example: ‘Serine 45 of beta catenine is phosphorylated
by a protein kinase”. When this phosphorylation is prevented by
mutation, cellular division is stimulated and cancer results. This would
be our hypothesis.

Thoroughness
demands us to propose a project with all the necessary experiments to
answer the question using our hypothesis as a focus in order to prove
it right or to demonstrate it wrong.

Being
rigorous in the formulation of a scientific research project implies
many aspects. A key component is choosing questions and hypothesis that
can be answered experimentally in the time and with the means proposed
in the project. Another main aspect is the rigor in the bibliographic
analysis of existing knowledge, mentioning the reports that favour our
hypothesis as well as those not supporting our ideas.

In
the methodological part, the selection of appropriate methods to carry
out experiments require great thoroughness and rigor. If a biological
model is adopted for our studies on cancer, we have to ask ourselves
how valid is this model ‘could the results be extrapolated to
human cancers?’ The methods that measure what we want to measure
must be chosen with utmost precision.

It
is always good and rigorous to use alternative methods to have independent
verifications and eliminate artefacts that can result from the use of
one method or technique. In the formulation of a project different approaches
are to be proposed and adapted to the different alternatives of eventual
results. A 3-4 years work project cannot be built totally depending
on whether the first experiment gives us a positive result.

Another
aspect that requires great honesty and thoroughness is precisely the
evaluation of research projects presented by our peers. We are judges
deciding on the financing of projects from which the careers of academics
and students depend and that may generate important advances to knowledge.

In
evaluating projects, we must forget who are our friends and enemies,
the competitions between Faculties and Universities and rigorously analyse
the project within its scientific context, in its relevance and in the
thoroughness in the approach of the authors. Every praise and criticism
we include in these evaluations should be validly supported.

Once
the project is approved and entering into execution, we again need rigor.

The
most creative and personal exercise of a scientific researcher is the
design of the experimental protocols. As a painter chooses his or her
paintbrushes and colours, researchers choose the number of samples,
the variation in the components, the tests that serve as negative controls,
those that act as positive controls demonstrating that everything works
as expected during the assay.

As
in art, there are protocols that are rustic, baroque, surreal or impressionistic.
It is magnificent that personality can find expression. Luis Federico
Leloir, the great Argentinian Nobel Prize winner told us that all his
experiments had only 3 test-tubes: one control and two experimental
samples and in this manner he discovered the mechanism of synthesis
of glycogen and won the Chemistry Nobel Prize. Young thesis students
generally want to answer all their questions at once in one experiment
with hundreds of tubes. In any case the adequacy of protocols will be
reflected by the fact that the whole design should pursue the ideal
of a straight answer. A clear and sound answer that says yes or no to
our question. The same as with the beauty pursued by artists, this ideal
of a clear and unambiguous answer is elusive and slips out of our hands.
We always find that the protocol left a small door open or a control
that was missing and we have to try it all over again more rigorously
until little by little we extract the small pieces of the truth we are
seeking for.

The
analysis of the results is another point that calls for rigor. How credible
are they? How general or specific? How statistically significant? Which
eventual interpretations are sustained by those results? Are there other
experiments that allow us to discriminate between those interpretations?

We
reach the critical stage in which we must communicate the new discoveries
we have learned from our researches. Until that moment, it has been
a personal exercise, a secret fight to extract a jewel, a new and unknown
truth from the womb of Nature.

However,
in order to be true research it must be communicated and put in a show
window, visible to our scientific peers for them to examine, to analyze,
to test.

Generally,
before publishing it, before putting it on the global show window, it
is useful and rigorous to show our results more privately to other colleagues
and friends. This may have several forms, for example, a Department
Seminar in which we orally present, a private consultation to a friend
that is in the same field of knowledge. Something much more advanced,
although yet preliminary, could be a free communication in a National
or International Congress.

To
make these presentations, where a very good review can be received,
it is however strategic to be ready to send a paper since many people
will know of our results and some unethical colleagues will try to publish
similar results.

The
final destiny of scientific research is publication and by the nature
this workshop, I imagine, the matter of rigor in publications is what
you are most interested in.

In
science, communication is essential since it is the interface between
the research authors and the rest of the world. Before they are communicated,
the results of the investigation are nonexistent, there is no contribution
to human culture, the answers to our questions that rose from our experiments
are only anecdotic.

This
communication has to be rigorous in order to comply with the main purpose
of publications: to present our results to the critical analysis of
our scientific peers, allowing our experiences be checked and expanded
by other researchers working on similar projects. This objective defines
the terms of the rigor in a scientific communication and, at the same
time, defines what scientific work is. Some time ago we discussed the
inclusion of publications of 1 page or less, or the summaries of scientific
meetings as valid publications in the CV’s of academics.

In
general, very brief publications, even though they are in journals with
qualified Editorial Committees cannot be considered as such since they
do not comply with the indispensable pre-requisite of offering enough
details on the methods and materials used to allow other people with
adequate training, to be able to repeat our experiences. This alerts
us against the current trend of many scientific journals of minimizing
the section on ‘materials and methods’.

Obviously,
in the case of ‘Abstracts’ of Congresses, they do not fulfil
another indispensable requirement: revision and approval by a Committee
of Peers of the Editorial Committee. Even though the Congress may have
had this Committee, a 200 word ‘Abstract’ cannot be seriously
evaluated regarding the scientific rigor of the research process and
of the analysis of the results.

Let
us see once again how each one of the components of a scientific publication
is influenced by rigor.

The
title must briefly reflect the essence of the results of the work. Rigor
restricts the amount of ‘merchandising’ in the titles. In
science there are words and areas that are fashionable, that call the
attention, that ‘sell’ better than others that are no longer
attractive. Obviously we want to attract many readers, but we cannot
fool them.

Often
a title offers us that we think we will find in the paper the solution
to many of our questions. Upon reading the full work, however, we notice
that the real contributions are much more modest and that the title
‘oversells’ the work done. Rigor is clearly missing.

In
the first page we also find a list of the authors. Ethics and rigor
require that all those that significantly contributed intellectually
to the work be included. The authors are co-responsible of everything
included in a publication and should share an adequate knowledge of
its content.

A
general rule establishes that any of the authors should be able to present
a half-hour seminar on the content of the publication. If one of the
authors is unable to do so, it is fair to ask oneself if he should really
be included among the authors. Clearly, technical staff, that play a
fundamental role in the execution of experiments should not be included
if they did not make an intellectual contribution to the design of the
protocols and to the interpretation of the results.

The
‘introduction’ should provide the reader a summary vision
of what was known in the field previous to its publication, recognizing
the significant contribution of other groups through the corresponding
bibliographical citations. In this part of the manuscript it is also
necessary to establish the question we made ourselves and briefly announce
the results we are going to be presenting.

The
section on ‘materials and methods’, as already expressed,
has to be rigorous in offering the necessary full experimental detail
to allow other scientists, with the necessary infrastructure and knowledge,
to repeat our experiments.

The
section ‘results’ is clearly the most important one in the
work. Rigor in its presentation requires the information of the number
of times the experiment was repeated and the variability obtained in
the results achieved. It is easy to mislead the inexperienced reader,
playing with the scales of the figures but these games clearly sin against
rigor.

Once
again, the text of the figures and tables require the inclusion of every
detail of the variables used, of the concentration of the components
and that these be expressed in values that are independent in the special
conditions in which our experiments are made (for example the calculation
of radioactivity in counts per minute depends on the efficiency of our
counter, etc.).

In
the section ‘discussion’, rigor implies presenting clearly
an objective interpretation of the results, saying in what measure progress
has been made in knowledge, including the different interpretations
our results have. It is licit to speculate on the possible meanings
of such results but we must clearly separate what we consider solidly
demonstrated from what is mere speculation on our part.

If
our results differ from others reported by other authors it is our duty
to point it out and be very careful and respectful while looking for
possible explanations for discrepancies.

In
the ‘bibliographical references’ it is once again essential
that quotes of papers of those works that are relevant to the field
of our publication be made correctly. It is necessary to moderate the
natural tendency of ‘self-quoting’ used to magnify the contributions
our group has made to the field. Some authors include in their quotes
all the works that they have ever previously published although they
have little to do with the subject of the manuscript.

But
scientific rigor in publications is not only on the side of the authors
of the papers but it also requires equal effort from the editorial committees
where they are presented.

A
paper is the result of an arduous work and a lot of sacrifices by a
group of people. Most scientific papers include invisibly years of work
and the efforts of thesis students and researchers, many hours of thought
and reflection, many funds spent on materials, equipment and reagents.
Along with the sheets or the bytes that reach a magazine’s editorial
office, comes the hope and ambitions of that group of authors of obtaining
a degree, of winning a fellowship or a project, or of being promoted
in their academic career and, of course, also of having made a contribution
to knowledge of that field.

It
is a great responsibility for the editors to provide that paper a fair
and exact evaluation, while on the other hand, it is their duty to keep
up the seriousness of science and its credibility. The whole magnificent
building of science and its extraordinary conquests require that the
knowledge published in well-known journals be reliable and serious.

All
of us who have been in the business for many years, have frequently
lost much time and effort trying to repeat without success some experiments
published in good journals.

There
is no better way to evaluate papers than sending them to expert peers
in the field. Fortunately most of them make a tremendous effort to provide
a balanced and constructive opinion of the papers revised. In my experience,
in almost all my publications, evaluators that have critically examined
my work have been right and contributed to the improvement of those
works. However, obviously, peers are human beings and as such they have
their prejudices and limitations.

I
am convinced that the papers that come from Chile or from another country
from the third world are revised by most of the editors with a different
attitude than those presented from Harvard, Cambridge or the University
of Paris. This hurts us, but we understand since we also review with
a different degree of credibility the papers that come from Africa,
Asia or another Latin American country compared to those coming from
more developed countries.

In
general, my experience as an editor is that those prejudices are balanced
out when one asks opinions from several evaluators. Obviously there
are cases in which the reviewers of papers do not do their job well
and deliver judgment without even having read the paper. All journals
should have black lists of this type of referees that don’t keep
up to the most elemental scientific rigor and seriously damage people.

While
reading some papers on scientific rigor I was surprised that there is
a certain debate on the relationship between rigor and relevance. Some
have even expressed that a dichotomy exists between those two words
that would define that if the work is relevant less rigor should be
expected. Others believe that both components are indispensable to make
the products of the investigation be useful or usable.

Frankly
I understood little of the debate and I think that it is simply a matter
of semantics on the meaning of the word ‘relevance’.

Likewise
there is in this debate a confusion on what is the execution of a research
project and what its communication implies.

If
we understand the word relevance as an adaptation to the interests of
the addressees of the communication of a scientific paper, we can recognize
there can be different levels of rigor in the communication of a scientific
work.

Clearly
a scientific work, for example on cancer and some molecular mechanisms
that underlie them, must be executed with the maximum scientific rigor.
However, the rigor of communication is going to be very different when
that same work is sent to a specialized journal (i.e.: Cancer Research)
than when it is presented as part of a symposium on cancer or when it
is delivered as a lecture to the general public. The strictness of the
details of methodology, controls and all the rest will be very different.
This is an important point we have to have in mind in defining the editorial
line of our journals.

If
they are highly specialized journals, the editors that are their gate
keepers, must establish a high grade of rigorousness as a requisite
in the papers since their readers are people from the field that want
to know all the details of the work . Journals focusing on review articles
on more general topics, will be less demanding on techniques and methodology,
emphasizing the more integrative ideas of the field.

We
must be conscious that even rigor in science can be exaggerated and
lead to paralyzing extremes. Some years ago, I met a person with excellent
training, already elderly, who paid so much attention to detail that
when weighing something he left the reagent on the analytical balance
for two hours until it reached the temperature of the balance. Then
his failing sight did not allow him to see correctly the numbers on
the scale. In the years I knew him, he never completed an experiment.

But
the best story on the extremes where the rigor in science can reach
is by Jorge Luis Borges in one of his extraordinary tales called precisely
‘Rigor in Science’ and I quote:

..In
that Empire, the Art of Cartography reached such Perfection that the
map of one Province alone took up the whole of a City, and the map of
the empire, the whole of a Province. In time, those Unconscionable Maps
did not satisfy, and the Colleges of Cartographers set up a Map of the
Empire which had the size of the Empire itself and coincided with it
point by point. Less Addicted to the Study of Cartography, Succeeding
Generations understood that this Widespread Map was Useless and not
without Impiety they abandoned it to the Inclemencies of the Sun and
of the Winters. In the deserts of the West some mangled Ruins of the
Map lasted on, inhabited by animals and Beggars; in the whole Country
there are no other relics of the Disciplines of Geography.

Suárez Miranda - Viajes de Varones Prudentes

Libro Cuarto, Capitulo XLV, LZrida, 1658

I
do not want to finish without mentioning a fundamental aspect on the
rigor in science. Rigor is one of the most important formative values
that science can give to Society.

We
are at a time when there is an open debate on the relationship between
science and society. This debate tries to define a new contract between
science and society at the time science and its product, knowledge,
has a huge impact on the social and economical development of people.

In
this new contract, society grants science and scientists freedom to
research in the fields established by their curiosity with the only
limitation of the ethics of their culture. Additionally, society grants
us financial and human resources to carry out these investigations and
gives us a certain degree of recognition.

What
do we give in exchange?

Obviously we provide the knowledge our investigations generate. Part
of that knowledge is quickly applicable and generates new technologies,
better and more competitive products. Another fraction of knowledge
is not yet applicable and is useful to increase the scientific and cultural
heritage of the world.

But
there is another contribution that science can give to Society that
has, by no means, less valuable. That contribution is given through
science education to children and young people in schools and high-schools.

A
high-quality science education, an education not centred in the teaching
of equations, formulas or definitions, but that makes students rediscover
the main principles of science through their own inquiries and experiments,
can make an enormous contribution to society. This contribution consists
in transmitting to children, the future citizens, a new rational way
to face the world and its problems with the values of science.

These
values, the search for truth, the rigor in their questions and in the
demonstrations and disrespect for dogmas and for authority for the sake
of authority, will contribute to make our citizens and our societies
more free, more progressive, more capable of solving their problems.

Scientific
rigor is a value that should penetrate our daily thoughts, our media,
the discourse of our politicians, and our complete culture.